SOP for Preparation of Nasal Spray Emulsions

Standard Operating Procedure for Preparation of Nasal Spray Emulsions

1) Purpose

The purpose of this SOP is to outline the procedures required for the preparation and quality control of nasal spray emulsions. These formulations consist of emulsified drug particles to ensure stability and efficient drug delivery to the nasal cavity.

2) Scope

This SOP applies to all personnel involved in the formulation, testing, and packaging of nasal spray emulsions at [Company Name]. It includes procedures for ingredient selection, emulsion preparation, quality control, and packaging.

3) Responsibilities

Operators: Responsible for weighing, mixing, emulsifying, and filling the nasal spray emulsions as per the batch manufacturing record (BMR).
Quality Assurance (QA): Ensures the emulsion meets the required stability, homogeneity, and particle size specifications.
Maintenance Team: Ensures that all equipment used in the emulsion preparation is cleaned, calibrated, and maintained.

4) Procedure

4.1 Preparation of Materials

4.1.1 Selection of Oil and Aqueous Phases

Select oils and aqueous components that are compatible with the API and suitable for nasal administration. Record the chosen components in the BMR.
Select surfactants to stabilize the emulsion. Common surfactants include polysorbates, lecithin, and sorbitan esters. Ensure that all components meet regulatory requirements.

4.1.2 Weighing of Ingredients

Weigh the required quantities of the oil phase, aqueous phase, surfactants, and API using a calibrated balance. Record the weights in the BMR, ensuring the accuracy is within ±2% of the target weight.

4.2 Emulsion Preparation

4.2.1 Emulsification Process

Heat the oil phase and aqueous phase separately to the required temperature (typically 40-50°C) as specified in the BMR. Use a temperature-controlled water bath if necessary.
Slowly add the oil phase to the aqueous phase while continuously stirring the mixture to form an emulsion. Use a high-shear mixer to homogenize the mixture and achieve the desired droplet size.
Continue mixing until the emulsion is uniform and stable. Record the mixing speed, time, and temperature in the BMR.

4.2.2 Homogenization

Further homogenize the emulsion using a homogenizer or high-pressure emulsification equipment. This step reduces droplet size to ensure uniformity and stability of the emulsion.
Test the droplet size using a particle size analyzer and record the results in the particle size testing log. The target droplet size for nasal emulsions is typically 1-5 microns.

4.3 Filling and Packaging

4.3.1 Filling Process

Transfer the homogenized emulsion into the nasal spray filling machine. Set the machine to fill the appropriate dose (e.g., 100 µL per spray) into sterile containers.
Test the fill accuracy by weighing 10 filled containers. The variation should not exceed ±5% of the target volume. Record the fill weights in the BMR.

4.3.2 Packaging

Seal the containers with sterile nasal spray nozzles or caps. Ensure that all containers are free of leaks or defects before final packaging.
Label the containers with the batch number, expiration date, and storage instructions. Package the containers in suitable secondary packaging to protect them from light and temperature fluctuations.

4.4 Quality Control Testing

4.4.1 Stability and Homogeneity Testing

Test the stability of the emulsion by monitoring the physical appearance (e.g., phase separation, color changes) over time. Store samples under controlled conditions (e.g., 25°C, 60% RH) and test at regular intervals (e.g., 1 month, 3 months, 6 months).
Test the homogeneity of the emulsion by taking samples from different points in the mixing vessel. Measure the concentration of the active ingredient using HPLC or UV spectrophotometry. Record the results in the homogeneity testing log.

4.4.2 Particle Size Testing

Test the particle size distribution of the emulsion using a laser diffraction particle size analyzer or dynamic light scattering. Ensure that the droplet size falls within the specified range (1-5 microns).
Document the results in the particle size testing log and ensure that the particle size distribution remains consistent over time.

4.5 Documentation

Document all steps of the formulation process in the BMR, including the weighing of ingredients, emulsification parameters, and filling process.
Record the results of quality control tests, including particle size, homogeneity, and stability testing, in the appropriate logs. QA personnel must review and sign off on the documentation before product release.

4.6 Equipment Cleaning and Calibration

After completing the batch, clean and sterilize all equipment used in the preparation of the nasal spray emulsion, including mixers, homogenizers, and filling machines. Follow the cleaning validation protocol.
Calibrate the equipment as per the calibration schedule. Record all cleaning and calibration activities in the respective logs.

5) Abbreviations, if any

API: Active Pharmaceutical Ingredient
QA: Quality Assurance
BMR: Batch Manufacturing Record

6) Documents, if any

Batch Manufacturing Record (BMR)
Particle Size Testing Log
Homogeneity Testing Log
Stability Testing Log
Cleaning Log
Calibration Log

7) References, if any

ICH Q1A – Stability Testing Guidelines
FDA Guidance on Nasal Drug Products

8) SOP Version

Version 1.0

Annexure

1. Particle Size Testing Log Template


  
    Date
    Formulation
    Particle Size (µm)
    Test Method
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Size
    Method
    Operator Name
    QA Name

Date	Formulation	Particle Size (µm)	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Size	Method	Operator Name	QA Name

2. Homogeneity Testing Log Template


  
    Date
    Formulation
    Test Point (Top/Middle/Bottom)
    API Concentration (%)
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Test Point
    Concentration
    Operator Name
    QA Name

Date	Formulation	Test Point (Top/Middle/Bottom)	API Concentration (%)	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Test Point	Concentration	Operator Name	QA Name

3. Stability Testing Log Template


  
    Date
    Formulation
    Storage Conditions
    Time Interval
    Stability Results
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Temperature and Humidity
    1 month, 3 months, etc.
    Pass/Fail
    Operator Name
    QA Name

Date	Formulation	Storage Conditions	Time Interval	Stability Results	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Temperature and Humidity	1 month, 3 months, etc.	Pass/Fail	Operator Name	QA Name

4. Cleaning Log Template


  
    Date
    Equipment ID
    Cleaning Procedure
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Equipment Name/ID
    Cleaning Method
    Operator Name
    QA Name

5. Calibration Log Template


  
    Date
    Equipment ID
    Calibration Procedure
    Calibration Results
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Equipment Name/ID
    Calibration Method
    Pass/Fail
    Operator Name
    QA Name

Date	Equipment ID	Cleaning Procedure	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Cleaning Method	Operator Name	QA Name

Date	Equipment ID	Calibration Procedure	Calibration Results	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Calibration Method	Pass/Fail	Operator Name	QA Name